The aim of the present study was to assess the short-term behavioral and physiological responses of piglets to different treatment protocols for the control of iron-deficiency anemia (IDA) and cystoisosporosis. Piglets were treated with either (1) an injection of iron combined with an oral application of toltrazuril (TLZ) by drenching or (2) a combination injection of TZL + gleptoferron; the behavior of the piglets was then evaluated. For this study, 288 piglets were divided into three experimental groups: 96 piglets were kept untreated (control group); 96 piglets received an oral administration of a generic TZL-based anticoccidial agent (20 mg/kg BW) along with intramuscular administration of iron dextran (200 mg/mL; 1 mL/piglet) at the same handling (oral + parenteral group, O + P); and 96 piglets received an intramuscular application of the combination product (parenteral group, P). For each treated piglet, the total handling time, flight reaction, and the intensity and frequency of vocalizations were determined using the methodology described by Scollo et al. (2020). Piglets in the O + P group were found to emit more screams during treatment administration than animals in the P group (21.05% vs. 8.42% of animals; p < 0.05). Piglets in the O + P group reacted worse to manipulation and oral administration because a higher percentage of animals continued to fidget even after handling (32.63% vs. 12.63%; p < 0.05). Differences in growth performance between the groups were not observed in our study (p > 0.05). In conclusion, the administration of a combination product reduced stress during administration, as indicated by reduced vocalizations and reactions to manipulation.

OBJECTIVE: Serum prealbumin is considered to be a sensitive predictor of clinical outcomes and a quality marker for nutrition support. However, its susceptibility to inflammation restricts its usage in critically ill patients according to current guidelines. We assessed the performance of the initial value of prealbumin and dynamic changes for predicting the ICU mortality and the effectiveness of nutrition support in critically ill patients.
METHODS: This monocentric study included patients admitted to the ICU between 2009 and 2016, having at least one initial prealbumin value available. Prospectively recorded data were extracted from the electronic ICU charts. We used both univariable and multivariable logistic regressions to estimate the performance of prealbumin for the prediction of ICU mortality. Additionally, the association between prealbumin dynamic changes and nutrition support was assessed via a multivariable linear mixed-effects model and multivariable linear regression. Performing subgroup analysis assisted in identifying patients for whom prealbumin dynamic assessment holds specific relevance.
RESULTS: We included 3136 patients with a total of 4942 prealbumin levels available. Both prealbumin measured at ICU admission (adjusted odds-ratio (aOR) 0.04, confidence interval (CI) 95% 0.01-0.23) and its change over the first week (aOR 0.02, CI 95 0.00-0.19) were negatively associated with ICU mortality. Throughout the entire ICU stay, prealbumin dynamic changes were associated with both cumulative energy (estimate: 33.2, standard error (SE) 0.001, p < 0.01) and protein intakes (1.39, SE 0.001, p < 0.01). During the first week of stay, prealbumin change was independently associated with mean energy (6.03e-04, SE 2.32e-04, p < 0.01) and protein intakes (1.97e-02, SE 5.91e-03, p < 0.01). Notably, the association between prealbumin and energy intake was strongest among older or malnourished patients, those suffering from increased inflammation and those with high disease severity. Finally, prealbumin changes were associated with a positive mean nitrogen balance at day 7 only in patients with SOFA <4 (p = 0.047).
CONCLUSIONS: Prealbumin measured at ICU admission and its change during the first-week serve as an accurate predictor of ICU mortality. Prealbumin dynamic assessment may be a reliable tool to estimate the effectiveness of nutrition support in the ICU, especially among high-risk patients.

Background: Helicobacter pylori is implicated in the development of gastritis, ulcers, and various gastric cancers, representing significant morbidity, mortality, and healthcare spending. Patients with H. pylori infection have traditionally been treated with oral antibiotics, however, oral therapy is not feasible in all clinical situations. We examined the available evidence supporting the use of intravenous (IV) antibiotics in H. pylori. Methods: This systematic review was carried out by reviewing multiple electronic databases: MEDLINE, CENTRAL, EMBASE, CINAHL, Clinicaltrials.org, and the World Health Organization (WHO) database of clinical trials. Articles published from database inception until February 12, 2023 that discussed the use of IV antibiotics in H. pylori management were included. Results: The search strategy identified 978 studies, with 11 meeting the inclusion criteria. The results demonstrate that there is a lack of robust trials examining the use of IV antibiotics in H. pylori management. Many trials demonstrated that IV antibiotics were safe and efficacious but the results are limited by inconsistencies in the year and geographic location trials were conducted, the IV and oral antibiotic regimens, and the duration of therapy. Conclusions: IV antibiotics appear to be a feasible therapeutic alternative in the management of H. pylori and can be considered, especially in patient populations where oral therapy is contraindicated.

Rheumatoid arthritis (RA) is an autoimmune disease suffered by millions of people worldwide. It can significantly affect the patient\'s quality of life by damaging not only the joints but also organs such as the lungs and the heart. RA is normally treated using nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), and biologics. These active agents often cause side effects and offer low efficacy due to their lack of specificity and limited retention time. In an attempt to improve RA treatments, hydrogel-based systems have been proposed as drug delivery carriers. Due to their exceptional adaptability and biocompatibility, hydrogels have the potential of enhancing the delivery of RA therapy through different administration routes in an efficient and effective manner. In this review, we explore the application of hydrogel systems as potential carriers in RA treatment. Additionally, we discuss recent work in the field and highlight the required hydrogel properties, depending on the administration route. The outstanding potential of hydrogel systems as carriers for RA was demonstrated; however, there is extensive research yet to be done to improve available treatments for RA.

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Outpatient parenteral antimicrobial therapy (OPAT) has been expanding in recent years and serves as a viable solution in reducing the shortage of hospital beds. However, the wider implementation of OPAT faces numerous challenges. This review aimed to assess implementation barriers and facilitators of OPAT services. Studies describing barriers and facilitators of the OPAT service were retrieved from PubMed, Scopus, MEDLINE, EMBASE, CINAHL, Cochrane Library, Web of Science Proceedings, International Pharmaceutical Abstracts and PsycINFO. All types of study designs published in the English language were included. Studies that did not mention any barrier or facilitator, did not differentiate OPAT and inpatient, focused on specific antimicrobials or diseases, and made no distinction between parenteral and other treatments were excluded. Qualitative analysis was performed using the \'best-fit\' framework approach and the Consolidated Framework for Implementation Research (CFIR). The review was PROSPERO registered (CRD42023441083). A total of 8761 studies were screened for eligibility and 147 studies were included. Problems in patient selection, lack of awareness, poor communication and co-ordination, lack of support, lack of structured service and inappropriate prescriptions were identified. OPAT provides safe, effective and efficient treatment while maintaining patients\' privacy and comfort, resulting in less daily life disruption, and reducing the risk of infection. Satisfaction and preference for OPAT were very high. Initiatives in strengthening OPAT such as antimicrobial stewardship and telemedicine are beneficial. Challenges to and facilitators of OPAT were identified among patients, health professionals, OPAT service providers and healthcare administrators. Understanding them is crucial to designing targeted initiatives for successful OPAT service implementation.

This Focus on Meetings contribution summarizes recent advances in the research on phospholipids and their applications for drug delivery and analytical purposes that have been presented at the hybrid Researcher\'s Day 2023 Conference of the Phospholipid Research Center (PRC), held on July 3-5, 2023, in Bad Dürkheim, Germany. The PRC is a non-profit organization focused on expanding and sharing scientific and technological knowledge of phospholipids in pharmaceutical and other applications. This is accomplished by, e.g., funding doctoral and postdoctoral research projects. The progress made with these projects is presented at the Researcher\'s Day Conference every two years. Four main topics were presented and discussed in various lectures: (1) formulation of phospholipid-based nanocarriers, (2) therapeutic applications of phospholipids and phospholipid-based nanocarriers, (3) phospholipids as excipients in oral, dermal, and parenteral dosage forms, and (4) interactions of phospholipids and phospholipid-based vesicles in biological environment and their use as analytical platforms.

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Lipid and/or polymer-based drug conjugates can potentially minimize side effects by increasing drug accumulation at target sites and thus augment patient compliance. Formulation factors can present a potent influence on the characteristics of the obtained systems. The selection of an appropriate solvent with satisfactory rheological properties, miscibility, and biocompatibility is essential to optimize drug release. This work presents a computational study of the effect of the basic formulation factors on the characteristics of the obtained in situ-forming particulates (IFPs) encapsulating a model drug using a 21.31 full factorial experimental design. The emulsion method was employed for the preparation of lipid and/or polymer-based IFPs. The IFP release profiles and parameters were computed. Additionally, a desirability study was carried out to choose the optimum formulation for further morphological examination, rheological study, and PBPK physiological modeling. Results revealed that the type of particulate forming agent (lipid/polymer) and the incorporation of structure additives like Brij 52 and Eudragit RL can effectively augment the release profile as well as the burst of the drug. The optimized formulation exhibited a pseudoplastic rheological behavior and yielded uniformly spherical-shaped dense particulates with a PS of 573.92 ± 23.5 nm upon injection. Physiological modeling simulation revealed the pioneer pharmacokinetic properties of the optimized formulation compared to the observed data. These results assure the importance of controlling the formulation factors during drug development, the potentiality of the optimized IFPs for the intramuscular delivery of piroxicam, and the reliability of PBPK physiological modeling in predicting the biological performance of new formulations with effective cost management.

Background and purpose: Addition of preservatives ensures microbial stability, especially in multidose containers of parenterally administered pharmaceuticals. These compounds can cause side effects, and particularly at the site of application, might elicit or facilitate pain. TRPA1 is a cation channel expressed in peripheral neurons which contributes to pain and inflammation and is sensitive to many irritants. The most commonly used preservatives, in particular with a focus on parenteral formulations, were investigated for their potential to activate TRPA1. Experimental approach: Sixteen preservatives were screened for mediating calcium influx in human TRPA1-transfected HEK293t cells. Untransfected cells served as control, results were further validated in mouse sensory neurons. In addition, proinflammatory mediators serotonin, histamine and prostaglandin E2 were co-administered to probe a potential sensitisation of preservative-induced TRPA1 activation. Key results: Butylparaben, propylparaben, ethylparaben, bronopol, methylparaben, phenylethyl alcohol and phenol induced a TRPA1-dependent calcium influx in transfected HEK293t cells at concentrations used for preservation. Other preservatives increased calcium within the used concentration ranges, but to a similar degree in untransfected controls. Serotonin, histamine, and prostaglandin enhanced TRPA1 activation of phenylethyl alcohol, bronopol, ethylparaben, propylparaben and butylparaben. Conclusion and implications: Systematic screening of common preservatives applied for parenterally administered drugs resulted in identifying several preservatives with substantial TRPA1 channel activation. This activation was enhanced by the addition of proinflammatory meditators. This allows selecting a preservative without TRPA1 activation, particularly in case of pharmaceuticals that could act proinflammatory.